Antibody–drug conjugates are rapidly moving from experimental later-line therapies toward potential treatment backbones across both non-small-cell lung cancer and small-cell lung cancer.
At ESMO Congress 2026, the lung ADC landscape extends well beyond the established HER2 story. TROP2, HER3, c-MET, integrin β6, B7-H3 and DLL3 are all represented, while bispecific ADCs are introducing another layer of target selection. More importantly, the questions being asked have changed.
Several of the most closely watched studies no longer ask whether an ADC produces responses in heavily pretreated disease. Instead, they ask whether an ADC can replace chemotherapy, outperform chemotherapy after targeted-therapy resistance, move into first-line combinations, or establish a new treatment class in SCLC.
Here are the 10 lung cancer ADCs to watch at ESMO 2026.
Sacituzumab Tirumotecan: TROP2 Moves Toward the Front Line
Target: TROP2
Also known as: sac-TMT, SKB264, MK-2870
Sacituzumab tirumotecan is arguably the most consequential lung cancer ADC on the ESMO 2026 programme because it appears in two phase III NSCLC presentations addressing very different treatment settings. In OptiTROP-Lung06 (LBA66), sac-TMT plus pembrolizumab is being compared with platinum-based chemotherapy plus pembrolizumab as first-line treatment for PD-L1-negative advanced nonsquamous NSCLC.
The importance of this trial is difficult to overstate: rather than adding an ADC after chemotherapy failure, OptiTROP-Lung06 asks whether a TROP2 ADC can effectively replace the conventional chemotherapy component of first-line chemoimmunotherapy. The second phase III presentation, OptiTROP-Lung04 (LBA67), reports final overall survival for sac-TMT versus platinum chemotherapy in EGFR-mutated NSCLC after progression on EGFR-TKI therapy.
Together, the two studies position sac-TMT at opposite ends of a major therapeutic question: can TROP2-directed cytotoxic delivery become a broader treatment backbone rather than simply another rescue therapy?
Read About Sacituzumab Tirumotecan on OncoDaily
Sigvotatug Vedotin: A Critical Test of Integrin β6
Target: Integrin β6
Study: SigVie-002, LBA68
Sigvotatug vedotin is an integrin β6-directed ADC being evaluated against docetaxel in previously treated nonsquamous NSCLC.
Its ESMO presentation will be particularly important because Pfizer has already disclosed that the phase III SigVie-002 trial did not demonstrate a statistically significant OS improvement in the overall population. However, a stronger numerical trend in both OS and PFS was observed among patients who had received only one previous systemic therapy line. That makes this a different kind of ADC story.
Rather than simply asking whether the drug is active, ESMO will help clarify whether the negative overall result reflects lack of sufficient efficacy, use too late in the disease course, or the possibility that a more carefully selected population could still benefit.
For ADC development generally, SigVie-002 is an important reminder that an attractive antigen and potent payload do not automatically translate into a survival advantage.
Izalontamab Brengitecan: Bispecific ADC Therapy After EGFR TKI
Targets: EGFR × HER3
Also known as: iza-bren, BL-B01D1
Study: PANKU-Lung01, LBA71
Izalontamab brengitecan represents one of the most interesting technological developments in the ADC field: bispecific targeting. Rather than targeting a single antigen, iza-bren recognizes both EGFR and HER3, potentially increasing tumor-cell engagement across heterogeneous resistant clones.
The phase III PANKU-Lung01 trial evaluates iza-bren in EGFR-mutated nonsquamous NSCLC after progression on a third-generation EGFR TKI. Earlier pooled clinical experience has already shown meaningful activity in heavily pretreated EGFR-mutated disease, providing the rationale for randomized phase III development.
The key question is whether bispecific ADC targeting can overcome the biological heterogeneity that develops after prolonged EGFR inhibition without requiring clinicians to identify one specific resistance alteration.
Read About Iza-Bren on OncoDaily
Ruzaltatug Rezetecan: HER3 Takes on Platinum Chemotherapy
Target: HER3
Also known as: SHR-A2009
Study: HERON-Lung01, LBA72
HER3 has become one of the most competitive ADC targets in EGFR-mutated NSCLC. Ruzaltatug rezetecan combines a HER3-directed antibody with the topoisomerase-I inhibitor rezetecan. At ESMO 2026, HERON-Lung01 will report interim phase III results comparing ruzaltatug rezetecan with platinum-based chemotherapy after progression on EGFR-TKI therapy.
The strategic rationale differs somewhat from resistance-directed combinations such as EGFR plus MET inhibition. HER3-directed ADC therapy may remain active across several different resistance states because it does not require identification of one particular downstream resistance mutation.
A positive phase III result would strengthen the argument that surface-antigen-directed ADC therapy can become a broadly applicable post-TKI strategy in EGFR-mutated disease.
Telisotuzumab Adizutecan: c-MET-Directed ADC Therapy
Target: c-MET
Also known as: Temab-A, ABBV-400
Presentation: 2658RO
Telisotuzumab adizutecan is a c-MET protein-targeting ADC and another example of how MET biology is being approached beyond conventional kinase inhibition. At ESMO 2026, investigators will present an overall survival analysis from the first-in-human study in nonsquamous NSCLC during the metastatic NSCLC rapid oral session.
The presentation deserves attention because c-MET has long been recognized as both a driver and a resistance pathway in lung cancer, yet optimal biomarker selection remains challenging.
The development of a MET-directed ADC raises a different possibility: exploiting cell-surface protein expression to deliver a potent payload even when the tumor is not necessarily dependent on MET signaling in the way required for a kinase inhibitor.
Read About Telisotuzumab Adizutecan on OncoDaily
Zocilurtatug Pelitecan: A DLL3 ADC Moves Into First-Line SCLC
Target: DLL3
Also known as: zoci, ZL-1310
DLL3 has rapidly become one of the most important therapeutic targets in SCLC. Zocilurtatug pelitecan is a DLL3-directed ADC that will have first global combination data presented at ESMO 2026 in first-line extensive-stage SCLC.
The phase Ib/Ic programme evaluates zoci with atezolizumab, with or without carboplatin, testing whether the ADC can become part of a first-line treatment backbone rather than being reserved for relapsed disease. The ESMO presentation is scheduled for October 26.
The study is particularly relevant because DLL3 is already clinically validated as a therapeutic target through T-cell-engager development. ADCs now offer a competing way to exploit the same antigen, potentially with different toxicity, logistics and CNS activity.
Risvutatug Rezetecan: B7-H3 Competition Intensifies in SCLC
Target: B7-H3
Also known as: Ris-Rez, HS-20093, GSK5764227
Risvutatug rezetecan is one of several B7-H3 ADCs competing for a place in SCLC. At ESMO 2026, the EMBOLD PanTumor-101 programme will provide global dose-optimization data in extensive-stage SCLC, while the phase III EMBOLD-SCLC-301 trial will also be represented as a trial-in-progress presentation.
This development comes after the B7-H3 target generated considerable interest in relapsed SCLC. The crucial question is no longer whether B7-H3 ADCs have activity. It is whether individual agents can differentiate themselves through response durability, CNS efficacy, ILD risk, hematologic toxicity and global reproducibility.
Ris-Rez is particularly important because it is already moving into global phase III development.
Read About Risvutatug Rezetecan on OncoDaily
Ifinatamab Deruxtecan: Updated Data After a Regulatory Setback
Target: B7-H3
Also known as: I-DXd
Study: IDeate-Lung01
Ifinatamab deruxtecan is another major B7-H3-directed ADC in SCLC. Updated results from the phase II IDeate-Lung01 study will be presented at ESMO 2026 as 3842P. The timing of the presentation is particularly notable.
In September 2026, Daiichi Sankyo and Merck voluntarily withdrew the US biologics license application seeking accelerated approval of I-DXd for previously treated ES-SCLC after discussions with the FDA indicated that the available data did not meet the requirements needed to support accelerated approval.
The ESMO update will therefore be viewed through a different lens than a typical phase II readout. Durability, survival, intracranial efficacy and toxicity will all be important in understanding the future position of I-DXd within an increasingly crowded B7-H3 ADC landscape.
Tambotatug Pelitecan: B7-H3 Expands Beyond SCLC
Target: B7-H3
Also known as: Tam-Peli, YL201, RG6919
Tambotatug pelitecan has already generated major interest in SCLC after the randomized phase III TAISHAN-302 study demonstrated improved survival versus topotecan in relapsed disease. At ESMO 2026, however, the story broadens into NSCLC.
The programme includes efficacy and safety data from a phase I study of tambotatug pelitecan in locally advanced or metastatic NSCLC, together with additional analysis of interstitial lung disease across phase I/II studies. That makes Tam-Peli especially interesting.
If strong activity extends from SCLC into NSCLC, B7-H3 could emerge not merely as an SCLC target but as a much broader thoracic oncology platform.
The ILD analysis will also matter because pulmonary toxicity could become one of the major differentiators among multiple topoisomerase-I ADCs competing in the same disease.
Read About Tambotatug Pelitecan on OncoDaily
SHR-4849: Another DLL3 ADC Enters the SCLC Race
Target: DLL3
Also known as: IDE849
SHR-4849 represents a second major DLL3 ADC strategy in SCLC. At ESMO 2026, long-term phase I results will be presented in relapsed SCLC and other neuroendocrine carcinomas as poster 3815P.
Its inclusion highlights how quickly the DLL3 field is becoming competitive. T-cell engagers have demonstrated that DLL3 can be successfully targeted in SCLC, but ADCs may offer a different balance of antitumor activity, treatment logistics and toxicity.
The longer follow-up at ESMO will therefore be important for determining whether early responses translate into durable disease control and whether the agent can justify movement into registrational development.
What the ADC Programme at ESMO 2026 Really Shows
The most striking feature of the ESMO 2026 lung ADC landscape is its diversity of targets. TROP2 is being tested as a broad cytotoxic platform in first-line and post-EGFR NSCLC. HER3 and EGFR×HER3 bispecific ADCs are competing for the post-EGFR-TKI setting.
c-MET-directed ADC therapy introduces a protein-expression strategy around a pathway already familiar from targeted resistance therapy. And in SCLC, B7-H3 and DLL3 have created two rapidly developing ADC ecosystems. The second major theme is movement earlier in treatment.
Sac-TMT is being tested as a replacement for chemotherapy in first-line NSCLC. Zocilurtatug pelitecan is already being combined with first-line immunotherapy in ES-SCLC. Other programmes are moving directly into phase III comparisons rather than spending years confined to late-line single-arm development. The third issue will be differentiation.
When several ADCs target the same protein, the target itself is no longer enough to distinguish them. Linker stability, payload, drug-to-antibody ratio, bystander effect, CNS penetration, ILD, hematologic toxicity and dose intensity may ultimately determine which molecule succeeds.
OncoDaily Takeaway
ESMO 2026 could mark a transition from the era of “an ADC for lung cancer” to an era of multiple competing ADC classes with distinct positions in the treatment algorithm.
In NSCLC, sacituzumab tirumotecan has perhaps the greatest immediate practice-changing potential because phase III studies are testing it both in first-line PD-L1-negative disease and after EGFR-TKI progression.
Izalontamab brengitecan and ruzaltatug rezetecan could reshape the increasingly crowded post-EGFR setting, while sigvotatug vedotin will provide an important lesson about where integrin β6 targeting may, or may not work.
In SCLC, the competition is even more intense. B7-H3 ADCs including risvutatug rezetecan, ifinatamab deruxtecan and tambotatug pelitecan, together with DLL3-directed zocilurtatug pelitecan and SHR-4849, are creating an entirely new therapeutic landscape.
The central question at ESMO will therefore not be simply whether ADCs have activity in lung cancer.
It will be:
Which target, which ADC, which line of therapy, and which toxicity profile is good enough to displace the current standard?
